Do expectations determine postoperative disability in women with endometriosis? Study protocol for a clinical mixed-methods observational cohort study.

INTRODUCTION: Overall, 20%-30% of women with endometriosis report endometriosis-related disability after successful laparoscopy. This indicates a potential impact of psychological factors, such as expectations, on treatment outcomes. It is already known that expectations determine treatment outcomes in various health conditions, such as cardiologic or gynaecology. Therefore, we investigate the impact of expectations and other psychological factors on patients' course of treatment outcomes after laparoscopy. METHODS AND ANALYSIS: A longitudinal mixed-methods study with N=300 women treated at a specialised centre of surgical endoscopy and endometriosis will be conducted with one preoperative and eight postoperative assessments of endometriosis-related disability and a priori specified predictors such as expectations.Additionally, two subsamples (each ~n=30) will be either interviewed about their endometriosis-related disability, expectations, and experiences of laparoscopy before and after surgery or asked once per day for 30 consecutive days using ambulatory assessments. Quantitative data will be analysed using multilevel modelling for longitudinal data. Structural content analysis will be used for qualitative data. DISCUSSION: To optimise treatment for women with endometriosis, it is essential to understand how treatment expectations and other psychological and medical factors influence treatment outcomes after laparoscopy. ETHICS AND DISSEMINATION: The Ethics Committee of the Psychotherapeutenkammer Hamburg, Germany, gave ethical approval (ROXWELL-2021-HH, 25 June 2021). TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT05019612).

Sexual functioning after total versus subtotal laparoscopic hysterectomy.

AIM: To evaluate postoperative sexual functioning and the influence of patients' expectations on the change in sexuality following laparoscopic total (TLH) versus subtotal hysterectomy (LASH). METHODS: A total of 120 women undergoing laparoscopic hysterectomy were preoperatively enrolled in this bicentric prospective study. Sexual functioning (SF) was evaluated using the female sexual function index (FSFI). Additionally, participants filled in a standardised questionnaire concerning expected changes in SF after surgery. At 3, 6 and 12 months following surgery, women were asked again to assess their level of SF (FSFI). Data of women who participated in at least one FSFI follow-up assessment were analysed (n = 92). We compared the change in SF after surgery between patients with TLH (n = 46) and LASH (n = 46). Additionally, we calculated regression analyses with the patients' expectations as a predictor for change in FSFI scores. RESULTS: Comparing the change of FSFI scores after surgery in both collectives revealed differences only 3 months after surgery, as improvement was stronger for the LASH collective compared to the THL group (p = 0.006). There were no changes comparing collectives after 6 (p = 0.663) and 12 (p = 0.326) months. Concerning patients' expectations, for the LASH group baseline SF (p < 0.001), but not expectations (p = 0.567) predicted the strength of change at each of the follow ups: a lower level of baseline SF was linked to a stronger improvement after surgery. For the THL collective, both baseline SF (p < 0.001) as well as patients' expectations (3 months: p = 0.077, 6 months: p = 0.37, 12 months: p = 0.024) predicted the strength of change: both, a lower level of baseline SF and higher expectations towards an improvement predicted a stronger improvement. CONCLUSION: The preservation of the cervix does not show an advantage in improving SF after surgery. Both methods induce a comparable improvement in long-time SF, especially in patients with an impaired sexuality pre-surgery. Furthermore, patients' expectations concerning this matter seem to have an impact on the postoperative outcome; therefore, this circumstance should be considered in future projects.

Role of Indocyanine Green in Fluorescence Imaging with Near-Infrared Light to Identify Sentinel Lymph Nodes, Lymphatic Vessels and Pathways Prior to Surgery - A Critical Evaluation of Options.

Modern surgical strategies aim to reduce trauma by using functional imaging to improve surgical outcomes. This reviews considers and evaluates the importance of the fluorescent dye indocyanine green (ICG) to visualize lymph nodes, lymphatic pathways and vessels and tissue borders in an interdisciplinary setting. The work is based on a selective search of the literature in PubMed, Scopus, and Google Scholar and the authors' own clinical experience. Because of its simple, radiation-free and uncomplicated application, ICG has become an important clinical indicator in recent years. In oncologic surgery ICG is used extensively to identify sentinel lymph nodes with promising results. In some studies, the detection rates with ICG have been better than the rates obtained with established procedures. When ICG is used for visualization and the quantification of tissue perfusion, it can lead to fewer cases of anastomotic insufficiency or transplant necrosis. The use of ICG for the imaging of organ borders, flap plasty borders and postoperative vascularization has also been scientifically evaluated. Combining the easily applied ICG dye with technical options for intraoperative and interventional visualization has the potential to create new functional imaging procedures which, in future, could expand or even replace existing established surgical techniques, particularly the techniques used for sentinel lymph node and anastomosis imaging.

Postoperative sexual functioning in total versus subtotal laparoscopic hysterectomy: what do women expect?

PURPOSE: To evaluate sexual functioning and expected changes in sexual functioning in women with planned total versus subtotal laparoscopic hysterectomy. METHODS: A total of 120 women undergoing laparoscopic hysterectomy were preoperatively enrolled in this study with a cross-sectional design. Full data sets were available for 112 patients, so that 56 patients with planned total laparoscopic hysterectomy (TLH) and 56 women with planned laparoscopic supracervical hysterectomy (LASH) were preoperatively assessed. Sexual functioning was evaluated using the female sexual function index (FSFI). Additionally, participants filled in a standardised questionnaire concerning expected changes on sexual function after the procedure. Demographic parameters, expectations concerning postoperative sexuality and FSFI scores were analysed and compared in women undergoing TLH and LASH. RESULTS: There were no significant differences concerning demographic parameters and FSFI scores comparing collectives. Sexuality in general was considered more important in women undergoing LASH (2.88 ± 0.83 vs. 2.48 ± 0.89; p = 0.011). Also, in 29 patients (52%) opting for LASH and 8 (14%) patients undergoing TLH a potential change in postoperative sexuality had an impact on their choice for a subtotal/total hysterectomy, respectively (p < 0.001). CONCLUSION: Patients' expectations concerning preservation of the cervix and postoperative sexuality appear to have the potential to bias investigations comparing total with subtotal hysterectomy. Hence, future research focusing on this issue should be accomplished incorporating patients' expectations stratified by mode of intervention.

Cosmetic outcome of skin adhesives versus transcutaneous sutures in laparoscopic port-site wounds: a prospective randomized controlled trial.

BACKGROUND: In an elective laparoscopic surgery, the cosmetic outcome becomes increasingly important. We conducted a study to evaluate the cosmetic outcome 3 months after a laparoscopic procedure and compared skin adhesive (SA) versus transcutaneous suture (TS). METHODS: A randomized, controlled, prospective study was conducted at a single study centre in Hamburg, Germany. Seventy-seven patients undergoing laparoscopic surgery with two lower abdominal port sites met the study requirements. It was decided randomly which port site would be closed with SA. The opposite site was closed with TS. Wounds were assessed after 7-12 days and after 3 months. Cosmetic outcome was measured by a visual analogue scale (VAS) completed by the patient, by the Hollander wound evaluation scale (HWES) and by the judgement of blinded investigators. RESULTS: Seventy-seven subjects were randomized. Complete data from the 3-month follow-up visit were available from 56 patients (72.7 %). The VAS scale ranged from 0 to 100 mm with "0" representing the best possible cosmetic outcome. Median satisfaction was 2 mm in the TS group and 3 mm in the SA group. The mean was high in both groups 4.6 (s = 13.1) versus 3.8 mm (s = 4.6). The outcome was neither clinically nor statistically significant. Cosmetic outcome was assessed by an investigator, and the HWES showed no difference. In regard to complications, no difference was found between SA and TS, either. CONCLUSIONS: In conclusion this study demonstrated that closure of laparoscopic port-site wounds leads to equivalent outcomes whether SAs or TSs are used. Complications are rare in both methods. Thus, SAs seem to be a valid alternative to sutures in laparoscopic surgery. Registration site: www.clinicaltrials.gov . REGISTRATION NUMBER: NCT02179723.

Aberrant expression of the pluripotency marker SOX-2 in endometriosis.

Expression of the pluripotency factors SOX-2, OCT-4, KLF-4, and NANOG was analyzed by quantitative real-time polymerase chain reaction, immunohistochemistry, and immunofluorescence microscopy in the endometrium, myometrium, and endometriotic tissue of 36 patients. Aberrant expression of SOX-2 may indicate a stem cell origin of endometriosis, whereas the presence of all progenitor markers in endometrial tissue marks the endometrium as a potential source for induced pluripotent stem cell generation.

The adult stem cell marker Musashi-1 modulates endometrial carcinoma cell cycle progression and apoptosis via Notch-1 and p21WAF1/CIP1.

The RNA-binding protein Musashi-1 has been proposed to maintain stem cell function during development and regenerative processes as a modulator of the Notch-1 signaling pathway. Musashi-1 expression is upregulated in endometrial carcinoma, however, its pathogenetic role in this tumor entity is unknown. Here we investigate the functional impact and mode of action of Musashi-1 on endometrial carcinoma cell behaviour in vitro. Aldehyde dehydrogenase-1 activity and side population (SP) measurement by Hoechst dye exclusion revealed that the Ishikawa endometrial carcinoma cell line contains a pool of putative cancer stem cells. Musashi-1 expression is 20.8-fold upregulated in SP+ compared to SP- and equally distributed between ALDH+ and ALDH- cell pools. siRNA-mediated knockdown of Musashi-1 mRNA expression lead to an altered expression of the signaling receptor Notch-1 and its downstream targets, the transcription factor Hes-1 and the cell cycle regulators p21(WAF1/CIP1) and cyclin B1, as determined by Western blotting and quantitative real-time PCR. Flow cytometric and ELISA analyses revealed that Musashi-1-mediated modulation of these factors exerted an antiproliferative effect on the cell cycle, and increased apoptosis in endometrial carcinoma cells. We conclude that Ishikawa cells contain a subpopulation of cells with stem cell-like properties. Musashi-1 modulates endometrial carcinoma cell cycle progression and apoptosis via the stemness-related factors Notch-1, Hes-1 and p21(WAF1/CIP1) , thus emerging as a novel future target for endometrial carcinoma therapy.

Ultrasonic technology: a new treatment option for anal condylomata acuminata.

PURPOSE: Treatment options for anal and perianal warts caused by human papillomavirus include topical application of cytotoxic substances or immunomodulators and ablative procedures. The objective of this prospective study was the evaluation of the ultrasound-driven Harmonic Scalpel (Ethicon Endo-Surgery, Norderstedt, Germany) for resection of anal and perianal condylomata acuminata. METHODS: Eight men and three women (age range, 26-72 years) with anal and perianal condylomata acuminata were treated by a Harmonic Scalpel blade operating at a vibration frequency of 55.5 kHz and within a temperature range of 65 degrees C to 120 degrees C. Nine patients were treatment naïve, and two patients had recurrent disease. Follow-up ranged from 4 to 26 months. RESULTS: Seven patients had perianal condylomata, two patients had exclusively intra-anal, and two patients had perianal and intra-anal warts. All condylomata were excised in a single-step procedure with complete clearing without injury of subepidermal layers. We observed no intraoperative or postoperative complications. No recurrences occurred during follow-up. CONCLUSIONS: The Harmonic Scalpel has been an effective and safe method for the treatment of anal perianal human papillomavirus condylomata without recurrent warts. Subepidermal skin levels remained uninjured; thus, no complications or unsatisfactory cosmesis occurred.

Chromosomal losses of regions on 5q and lack of high-level amplifications at 8q24 are associated with favorable prognosis for ovarian serous carcinoma.

In this study, we describe characteristic chromosomal alterations in a consecutive series of 96 serous ovarian tumors by comparative genomic hybridization. We analyze their association with different pathways of progression, histological grade, and clinical outcome. The most striking difference between low-grade and high-grade serous carcinomas was seen in a higher incidence of chromosomal gains at 3q and 20q and losses of 13q in the high-grade carcinomas. In addition, high-level amplifications were significantly more frequent in high-grade carcinomas, specifically involving regions on 3q and 8q. Chromosomal amplifications of 19p and 19q and losses of 4q and 5q were among the most frequent changes found in both low-grade and high-grade carcinomas, distinguishing them from borderline tumors, which had very few recurrent alterations. The most significant impact on survival of patients with invasive carcinomas Stage II-IV was observed for high-level amplifications of regions on 8q (mean overall survival (OS) 69 versus 27 months, P = 0.0006). Interestingly, low-level gains on 8q do not show any impact compared to cases with no alteration. Surprisingly, chromosomal losses on 5q had a protective impact (mean OS 36 versus 76 months, P = 0.0007). Combination of both parameters resulted in two risk groups. Low risk: loss on 5q, no amplification on 8q (mean OS 84 months); high risk: no loss on 5q, amplification on 8q (mean OS 26 months). This difference is even more pronounced, if only cases with residual tumor of less than 2 cm are included, resulting in a 5-year survival of 100% and 0% (P = 0.0005).

Detection of peritoneal endometriotic lesions by autofluorescence laparoscopy.

OBJECTIVE: This study was undertaken to evaluate the feasibility of autofluorescence laparoscopy in the diagnosis of endometriotic lesions. STUDY DESIGN: Prospective analysis of 83 consecutive patients undergoing laparoscopy for suspected endometriosis under white light illumination and autofluorescence diagnosis. The study measured total number of endometriotic lesions diagnosed under white light illumination and with autofluorescence diagnosis. RESULTS: The biopsy-based sensitivity of white light diagnosis alone and white light illumination and autofluorescence for detecting nonpigmented peritoneal endometriotic lesions was 65% compared with 92% (1.42-fold increase). The corresponding specificity was 68% as opposed to 84%. Occult areas of endometriosis were discovered using autofluorescence diagnosis. Statistical analysis was performed with chi2 test and McNemar test. CONCLUSION: Combination of white light illumination and autofluorescence is significantly superior to white light illumination alone in detecting nonpigmented endometriotic lesions. Autofluorescence diagnosis of nonpigmented endometriotic lesions may become an alternative to fluorescence diagnosis after application of 5-aminolevulinic acid, especially because of no side effects.

COX-2 overexpression in peritoneal lesions is correlated with nonmenstrual chronic pelvic pain.

OBJECTIVE: To investigate cyclooxygenase (COX-2) expression within different endometriotic lesions and to assess whether these expression patterns correlate with clinical characteristics. DESIGN: Retrospective cross-sectional study. SETTING: University Hospital. PATIENTS: Seventy patients with histologically confirmed exclusively peritoneal (n=20), ovarian (n=19) or deep-infiltrating (n=31) endometriosis and a detailed medical history. INTERVENTION: Immunohistochemical analysis for COX-2 was performed on 108 endometriotic lesions. MEASUREMENTS AND MAIN RESULTS: COX-2 intensity, percentage of stained glandular endometriotic cells, and correlation of COX-2 expression with clinicopathological parameters. Semiquantitative COX-2 expression did not differ between distinct morphological types of endometriosis and showed no association with the menstrual cycle. Patients with peritoneal-only endometriosis suffering from moderate or severe chronic pelvic pain showed significantly more frequent COX-2 overexpression than asymptomatic patients or patients with minimal symptoms. In patients with exclusively ovarian or deep-infiltrating endometriosis no association between COX-2 expression and clinical parameters, such as chronic pelvic pain, dysmenorrhoea, dyspareunia, sterility, lower urinary tract symptoms or gastrointestinal symptoms was observed. CONCLUSION: Peritoneal endometriotic lesions with increased COX-2 expression have a special relevance for the development of chronic, nonmenstruation-associated, pelvic pain in endometriotic patients. These patients may benefit from therapy with COX-2 inhibitors.

Interobserver variability in the diagnosis of minimal and mild endometriosis.

STUDY OBJECTIVE: To evaluate the observer's influence on the diagnosis and classification of endometriosis according to the rASRM classification. DESIGN: : Prospective analysis. SETTING: University hospital. PATIENTS: Digital videotapes of laparoscopies in three patients with typical endometriotic disorders (rASRM I, II and no endometriosis). INTERVENTION: One hundred and eight gynecologic surgeons were asked to indicate the endometriotic lesions on a prepared surgical sketch and to classify the site according to the rASRM classification. MEASUREMENTS AND MAIN RESULTS: Total number, location and morphology of endometriotic lesions, rASRM classification. The interobserver correlation concerning the number of lesions ranged between 18% (rASRM II) and 30%. (rASRM I). There was marginal correlation regarding the location of endometriotic lesions. Kendall W coefficient ranged from 0.14 (rASRM II) to 0.44 (rASRM I) (p < 0.001). Only 13% (rASRM II) to 22% (rASRM I) of observers used the correct endometriotic classification. None of the participants specified the morphological characteristics of endometriotic lesions according to the rASRM classification. CONCLUSION: Visual assessment of an operative situs with minimal and mild endometriosis is subject to a considerable interindividual variability. One and the same lesion is assessed quite differently by different observers. Histopathological verification seems to be necessary to objectify the diagnosis of endometriosis.

Laparoscopy in patients over 60 years old: a prospective, randomized evaluation of laparoscopic versus open adnexectomy.

OBJECTIVE: To compare objective and subjective parameters of surgical stress following laparoscopic and open adnexectomy in patients older than 60 years old. STUDY DESIGN: Twenty patients with a benign ovarian tumour were prospectively randomized to undergo adnexectomy by a laparoscopic or an open surgical procedure. Measurements included C-reactive protein; interleukin-6 before, during, and after surgery; intensity and duration of postoperative pain; and complications and recovery period. Statistical analysis consisted of analysis of variance and a Mann-Whitney U test. RESULTS: The levels of the interleukin-6 and C-reactive protein differed significantly between the 2 operative procedures (P = .013) in favor of the laparoscopic approach. The laparoscopic approach was associated with a reduction in operative morbidity, postoperative pain, analgesic requirement, and recovery period. CONCLUSIONS: Minimally invasive surgery is of particular benefit to elderly patients if there is a plan in place for appropriate staging and treatment by laparotomy for malignancy. It should be the first choice and may help to reduce postoperative complications.

Detection of nonpigmented endometriotic lesions with 5-aminolevulinic acid-induced fluorescence.

STUDY OBJECTIVE: To evaluate the feasibility of fluorescence diagnosis of nonpigmented (red and white) endometriotic lesions with 20 mg/kg of 5-aminolevulinc acid (5-ALA) 5-7 and 10-14 hours before surgery. DESIGN: Prospective analysis (Canadian Task Force classification II-2). SETTING: University hospital. PATIENTS: Twenty-four consecutive patients with suspected endometriosis undergoing laparoscopy. INTERVENTION: Laparoscopic surgery under white light illumination and fluorescence diagnosis. MEASUREMENTS AND MAIN RESULTS: The total number of endometriotic lesions detected under white light illumination was compared with the number of lesions detected with fluorescence diagnosis. Fluorescence diagnosis yielded an overall improvement of 35% in the detection of nonpigmented endometriotic lesions compared with white light illumination. Sensitivity (91%) and specificity (79%) were similar 5-7 and 10-14 hours before surgery. CONCLUSION: The dosage of 20 mg/kg body weight of 5-ALA is feasible for fluorescence diagnosis of nonpigmented endometriosis. Sensitivity of fluorescence diagnosis with 20 mg/kg is similar to that achieved with a 30-mg/kg dose. Sensitivity does not change within the application period 5-7 and 10-14 hours before surgery.